TY  - JOUR
A1  - Bugai, Andrii
A1  - Quaresma, Alexandre J. C.
A1  - Friedel, Caroline C.
A1  - Lenasi, Tina
A1  - Düster, Robert
A1  - Sibley, Christopher R.
A1  - Fujinaga, Koh
A1  - Kukanja, Petra
A1  - Hennig, Thomas
A1  - Blasius, Melanie
A1  - Geyer, Matthias
A1  - Ule, Jernej
A1  - Dölken, Lars
A1  - Barborič, Matjaž
T1  - P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress
T2  - Molecular Cell
N2  - DNA damage response (DDR) involves dramatic transcriptional alterations, the mechanisms of which remain ill defined. Here, we show that following genotoxic stress, the RNA-binding motif protein 7 (RBM7) stimulates RNA polymerase II (Pol II) transcription and promotes cell viability by activating the positive transcription elongation factor b (P-TEFb) via its release from the inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP). This is mediated by activation of p38MAPK, which triggers enhanced binding of RBM7 with core subunits of 7SK snRNP. In turn, P-TEFb relocates to chromatin to induce transcription of short units, including key DDR genes and multiple classes of non-coding RNAs. Critically, interfering with the axis of RBM7 and P-TEFb provokes cellular hypersensitivity to DNA-damage-inducing agents due to activation of apoptosis. Our work uncovers the importance of stress-dependent stimulation of Pol II pause release, which enables a pro-survival transcriptional response that is crucial for cell fate upon genotoxic insult.
KW  - Pol II elongation
KW  - Pol II pause release
KW  - P-TEFb
KW  - CDK9
KW  - 7SK snRNP
KW  - RBM7
KW  - genotoxic stress
KW  - DNA damage response
KW  - p38 MAP kinase
KW  - apoptosis
Y1  - 2019
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/22172
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-221726
VL  - 74
ER  -